CN106470748A - There is the sound field device of piezoelectric transducer array - Google Patents

There is the sound field device of piezoelectric transducer array Download PDF

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Publication number
CN106470748A
CN106470748A CN201580036600.6A CN201580036600A CN106470748A CN 106470748 A CN106470748 A CN 106470748A CN 201580036600 A CN201580036600 A CN 201580036600A CN 106470748 A CN106470748 A CN 106470748A
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fluid
piezoelectric
piezoelectric element
granule
transducer
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巴特·利普肯斯
杰森·迪翁
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Flodesign Sonics Inc
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D21/00—Separation of suspended solid particles from liquids by sedimentation
    • B01D21/28—Mechanical auxiliary equipment for acceleration of sedimentation, e.g. by vibrators or the like
    • B01D21/283—Settling tanks provided with vibrators
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D43/00—Separating particles from liquids, or liquids from solids, otherwise than by sedimentation or filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B06—GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS IN GENERAL
    • B06B—METHODS OR APPARATUS FOR GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS OF INFRASONIC, SONIC, OR ULTRASONIC FREQUENCY, e.g. FOR PERFORMING MECHANICAL WORK IN GENERAL
    • B06B1/00—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency
    • B06B1/02—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy
    • B06B1/06—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B06—GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS IN GENERAL
    • B06B—METHODS OR APPARATUS FOR GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS OF INFRASONIC, SONIC, OR ULTRASONIC FREQUENCY, e.g. FOR PERFORMING MECHANICAL WORK IN GENERAL
    • B06B1/00—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency
    • B06B1/02—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy
    • B06B1/06—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction
    • B06B1/0607—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction using multiple elements
    • B06B1/0622—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction using multiple elements on one surface
    • B06B1/0625—Annular array
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/02—Separating microorganisms from the culture medium; Concentration of biomass
    • H—ELECTRICITY
    • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10N—ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10N30/00—Piezoelectric or electrostrictive devices
    • H10N30/80—Constructional details
    • H10N30/88—Mounts; Supports; Enclosures; Casings
    • H10N30/883—Additional insulation means preventing electrical, physical or chemical damage, e.g. protective coatings

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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
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  • Mechanical Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sustainable Development (AREA)
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  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Investigating Or Analyzing Materials By The Use Of Ultrasonic Waves (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Transducers For Ultrasonic Waves (AREA)

Abstract

A kind of device for separating granule from fluid stream, including flow chamber, it has at least one entrance and at least one exports.At least one ultrasonic transducer, on the wall of flow chamber.Ultrasonic transducer includes the piezoelectric-array with least two piezoelectric elements.Piezoelectric-array includes piezoelectric, for producing multi-dimensional standing-wave in flow chamber.Reflector be located at flow chamber in the wall of at least one ultrasonic transducer opposite side on.

Description

There is the sound field device of piezoelectric transducer array
Background technology
The application is that the part of the U.S. Patent application of serial number 14/026,413 of September in 2013 submission on the 13rd continues again Application, the part of its U.S. Patent application of serial number 13/844,754 submitted to on March 15th, 2013 continues to apply for again, should Application claims the benefit of the right of following applications：The U.S. Provisional Patent Application sequence number 61/611,159 that on March 15th, 2012 submits to, The same U.S. Provisional Patent Application sequence number 61/611 submitted on March 15th, 2012,240, and on January 21st, 2013 submission U.S. Provisional Patent Application sequence number 61/754,792.Here, the content of these applications is expressly incorporated herein in entirety by reference.
In numerous applications, it is required for particle/fluid mixture is separated into the ability of its each ingredient.Sound is swum Using high intensity sound wave, and separate without a kind of granule that film or physical size exclude filtrate.It is known that work as depositing in fluid In density and/or compressible difference, granule to apply active force in the sound standing wave energy convection cell of high intensity, this density And/or compressible difference is also referred to as coefficient of correlation.The pressure distribution of standing wave includes the local pressure amplitude at node Smallest region and the maximum of the local pressure amplitude at antinode area.Density according to granule and compressibility, these granules can be caught Obtain at the node of standing wave or antinode.The frequency of standing wave is higher, can capture particle size by the pressure of standing wave less.
For multi-component liquor stream, it is desirable to have the isolation technics of effect, it can Waste reduction and reduce required energy Amount, thus the environment promoting sustainable development.
Content of the invention
Present disclosure is related to be preferably used for system and the device of extensive sound swimming.This device uses one as described herein Or multiple unique ultrasonic transducer.Transducer includes the rectangular array being made up of multiple piezoelectric elements.Producing multi-dimensional standing-wave Frequency under drive transducer.
Device disclosed in multiple embodiments of this paper, for from substrate fluid separate second fluid or Granule, it includes：There is at least one entrance and the flow chamber of at least one outlet；What at least one was located on flow chamber wall ultrasonic changes Energy device, ultrasonic transducer includes the piezoelectric-array being formed by multiple piezoelectric elements, and it can be under the driving of voltage signal, in stream Form multidimensional sound standing wave in room；And at least one reflector, it is located at the flow chamber wall on the opposite of at least one ultrasonic transducer On.Axial sound power is identical with the order of magnitude of lateral sound power amplitude.Second fluid or particle agglomeration are in the pressure wave of multidimensional sound standing wave At section (acoustic radiation potential energy minimum point), and due to Gravity Separation, constantly drop out from multidimensional sound standing wave, or due to buoyancy, Constantly emersion from multidimensional sound standing wave.
In some embodiments, piezoelectric-array (piezoelectric array) is present on monocrystal silicon, by one Or a plurality of raceway groove makes each piezoelectric element be separated from each other.One or more raceway groove there may be have different from piezoelectric Embedding Material (potting material).Embedding Material can be polymer, such as epoxy resin (epoxy).
In other implementations, by Embedding Material, the piezoelectric element physics of each piezoelectric element and surrounding is divided From.Embedding Material can be polymer, such as epoxy resin.
Piezoelectric-array can be rectangular array.Each piezoelectric element can be of the same size.Each piezoelectric element can To be independently connected with respective electrode pair.
In specific embodiment, special-shaped ozzle wall (contoured nozzle wall) be located at flow chamber at least one The upstream of entrance.
Further disclose and separate second fluid or granule method from substrate fluid, it includes：Make substrate fluid and Second fluid or granule mixture flows through device, and this device includes：There is at least one entrance and at least one exports Flow chamber；At least one ultrasonic transducer being located on flow chamber wall, ultrasonic transducer includes the pressure being formed by multiple piezoelectric elements Electric array, it can form multidimensional sound standing wave under the driving of voltage signal in flow chamber；And at least one reflector, its On the flow chamber wall on the opposite of at least one ultrasonic transducer；And stayed to piezoelectric-array transmission voltage signal with forming multidimensional sound Ripple, it is resisted liquor stream and captures second liquid or granule and allow to reunite, thus the size of second fluid or granule increases, and leads to Cross Gravity Separation constantly to drop out from multidimensional sound standing wave.Can will clear away from room through detached material, receive by liquor stream Collect in container or make its volume less by compression.
Granule can be Chinese hamster ovary (CHO) cell, NS0 hybridoma, baby hamster kidney (BHK) cell or human body Cell.
Sometimes, the mutual out-phase of piezoelectric element is run.Other when the mutual inphase operation of piezoelectric element.
Substrate fluid can be at least 25mL/min by the flow velocity of flow chamber.Piezoelectric element can be in 100kHz to 20MHz Under certain frequency in scope run, or, in specific embodiment can in about 2MHz to 2.5MHz scope certain frequency Run under rate.
In most cases, the multi-dimensional standing-wave of generation leads to the acoustic radiation with axial force and lateral force component Power, and axial force component is identical with the order of magnitude of side force component amplitude.
Piezoelectric-array is present on monocrystal silicon, so that each piezoelectric element is separated from each other by one or more raceway groove.One There may be in bar or a plurality of raceway groove has the Embedding Materials different from piezoelectric.
In other implementations, by Embedding Material, the piezoelectric element physics of each piezoelectric element and surrounding is divided From.Each piezoelectric element can be independently connected with respective electrode pair.
These and other non-limiting parameters will be described in greater detail hereinafter.
Brief description
The brief description of accompanying drawing is presented herein below, these accompanying drawings are shown for illustrative exemplary enforcement described herein Example, and it is not intended to limit the present invention.
Figure 1A is schematic diagram, when illustrating that second fluid or grain density are less than substrate fluid density, the work(of sound swimming separator Energy.
Figure 1B is schematic diagram, when illustrating that second fluid or grain density are more than substrate fluid density, the work(of sound swimming separator Energy.
Fig. 2 is the cross-sectional view of conventional ultrasonic transducer.
Fig. 3 A is the sectional view of ultrasonic transducer structures used in present disclosure.There is air gap in transducer, and There is no backing layer or wearing plate.
Fig. 3 B is the sectional view of ultrasonic transducer structures used in present disclosure.There is air gap in transducer, and There are backing layer and wearing plate.
Fig. 4 is the entirety piezoquartz of Conventional monolithic used in ultrasonic transducer.
Fig. 5 is the exemplary Rectangular piezoelectric array with 16 piezoelectric elements, and it is used for the transducer of present disclosure.
Fig. 6 is the Rectangular piezoelectric array with 25 piezoelectric elements of another exemplary, and it is used for the transducer of present disclosure.
Fig. 7 is chart, illustrate acoustic radiation force, gravity-buoyancy and Stokes (Stokes ') resistance and particle size it Between relation.The unit of transverse axis is micron (μm), and the unit of the longitudinal axis is newton (N).
Fig. 8 is for the square transducer being driven at different frequencies, the amplitude of its electrical impedance and the figure of frequency Picture.
Fig. 9 A shows the captured line configuration of seven minimum amplitude points in fluid flow direction in Fig. 8 for the Subnormal subgroup.
Fig. 9 B is the perspective view illustrating separator.Also show fluid flow direction and captured line.
Fig. 9 C is from fluid intake, along the view of fluid flow direction (arrow 114) Fig. 9 B, shows the capture ripple of standing wave Section, can be with trapped particle at these node.
Fig. 9 D is along the arrow 116 shown in Fig. 9 B, towards captured line configuration, the view observed through transducer.
Figure 10 A illustrates the sound swimming separator for separating buoyant material.
Figure 10 B is the zoomed-in view of flow of fluid near special-shaped ozzle wall 129 and the junction of collecting pipe 137.
Figure 11 A shows the decomposition view of sound swimming separator used in bio-pharmaceuticals application.
Figure 11 B shows the decomposition view of the stacked-up type sound swimming separator with Liang Ge sound chamber.
Figure 12 A is to illustrate to use Beckman Kurt cell viability analyser (Beckman Coulter with regard to an experiment Cell Viability Analyzer) the efficiency chart picture of removal cell from medium.
Figure 12 B is to illustrate to use Beckman Kurt cell viability analyser (Beckman with regard to another experiment Coulter Cell Viability Analyzer) the efficiency chart picture of removal cell from medium.
Figure 13 shows the schematic diagram of the two-dimensional mathematical model for ultrasonic transducer and transducer array simulating developer.
Figure 14 A to Figure 14 D is the comparison diagram of Figure 13 numerical model result (bottom) and public data (top), shows numerical value The degree of accuracy of model.Figure 14 A compares momentum energy U.Figure 14 B compares the x-component of acoustic radiation force (ARF).The y that Figure 14 C compares ARF divides Amount.Figure 14 D compares the absolute value of ARF.
Figure 15 is the image of the sound standing wave amplitude being produced by overall piezoquartz in the model be shown in Figure 13.Frequency is 2.245MHz.Transverse axis is the position along X-axis, and the longitudinal axis is the position along Y-axis between transducer and reflector.
Figure 16 is the image of the sound standing wave amplitude being produced by 4 element piezoelectric-arrays in the model be shown in Figure 13.Frequency is Phase contrast between 2.245MHz, and each element is in change.
Figure 17 is the image of the sound standing wave amplitude being produced by 4 element piezoelectric-arrays in the model be shown in Figure 13.Frequency is Phase contrast between 2.245MHz, and each element is in change.
Figure 18 is the sound swimming configuration figure with 4x4 piezoelectric-array, and this 4x4 piezoelectric-array is made up of 2MHz PZT-8 crystal, It is formed with otch, as shown in Figure 5 in crystal.
Figure 19 is the comparison of the emulation of out-phase piezoelectric-array and the actual piezoelectricity experiment using out-phase array.For this emulation, Out-phase refers to conveyed voltage phase angle.For out-phase test, the phase place of numerical model changes from 0 ° 180 ° 0 ° 180 °.Right In experiment test, element changes under checker board pattern (checkerboard pattern).
Figure 20 is the comparison of the emulation of homophase piezoelectric-array and the actual piezoelectricity experiment using homophase array.For this emulation, Homophase refers to conveyed voltage phase angle.For homophase test, the phase place between all elements keeps constant.
Figure 21 is to illustrate that otch crystal (kerfed crystal) (top) is connected together by Embedding Material with having The transducer array (bottom) of piezoelectric element comparison diagram.
Figure 22 is the image illustrating the out-phase pattern test for 4 element arrays.
Figure 23 is the image illustrating the out-phase pattern test for 5 element arrays.
Figure 24 is the image of the normalization acoustic radiation force (ARF) in overall piezoquartz emulation.
Figure 25 is the image of ARF component (lateral and axial direction) ratio in overall piezoquartz emulation.
Figure 26 is the image of the normalization acoustic radiation force (ARF) in the 5 element emulation have variation phase.
Figure 27 is the image of ARF component (lateral and axial direction) ratio in 5 element emulation.
Figure 28 is to be shown in out-phase test, the image of array phase.In testing, dark element has 0 ° of phase angle, The element of light color has 180 ° of phase angles.
Specific embodiment
By referring to the specific descriptions hereafter expecting embodiment and wherein included embodiment, geography can be easier Solution present disclosure.Be described below and claims in, refer to many terms, under these terms should be defined as having Row meaning.
" one ", " a kind of " and " being somebody's turn to do " of singulative includes a plurality of referent, indicates unless the context otherwise.
Term "comprising" is used herein as needing the presence of part/step that certain indicates and allows other parts/step Rapid presence.Term "comprising" should be interpreted that include term " by ... form " implication, and from indicate part/ Impurity in the production process of step, term " by ... form " presence of part/step that only allows to indicate.
Numerical value should be understood to including：It is identical numerical value during the significance bit being reduced to equal number, and, according to than this The mode that the experimental error of the conventional measurement technology of type described in application is little deviates the value being previously mentioned to determine the numerical value of this value.
All scopes described herein all include cited end points, and can independently combinable (for example, " and from 2 grams to 10 grams " scope include 2 grams and 10 grams of end points and all intermediate values).
Term " substantially " and " about " can be used for can becoming including on the premise of the basic function not changing numerical value Dynamic numerical value.When being used in conjunction with scope, " substantially " and " about " equally discloses the absolute value of two end points, for example, " about 2 To about 4 " equally disclose scope " from 2 to 4 ".Term " substantially " and " about " can refer to the indication numeral that adds deduct 10%.
It should be noted that many terms are relative terms as used herein.For example, term "up" and "down" is in position On be relative to each other, it is, in given orientation, upper assembly is located at the height above sea level higher than lower assembly, but if making Device reverses, then these terms may change.Term " entrance " and " outlet " are with respect to it for given structure For the fluid that flows, for example, fluid flows to this structure by entrance, and flows out this structure by outlet.Term " on Trip " and " downstream " are to flow through for the direction that different assemblies are located with respect to fluid, it is, fluid is flowing through downstream components Flow through upstream component before.It should be noted that in the loop, first assembly both can be described as the upstream of the second assembly, also may be used To be described as the downstream of the second assembly.
Term " horizontal " and " indulging " are used for indicating the direction with respect to absolute standard, i.e. ground level.Term " on " and " it Under " or " upwards " and " downward " be also for absolute standard；Flow up the gravitation always against (opposing) earth.
The application is related to " equal magnitude ".If plurality is less than 10 value divided by the business compared with decimal, two numbers are Equal magnitude.
The sound swimming isolation technics of present disclosure are captured to the granule in substrate fluid or second fluid using ultrasonic standing wave (i.e. remains stationary).According to granule or second fluid with respect to substrate fluid sound reduced factor, granule or second fluid are many Concentrate at the node of dimension sound standing wave or antinode, form cluster, (for example pass through coalescence or poly- when these clusters rise to sufficiently large size Collection) with overcome multidimensional sound standing wave retentivity when, these clusters eventually drop out multidimensional sound standing wave.This is important with conventional method Difference, in conventional method, the track of granule is only changed by the effect of acoustic radiation force.The scattering that sound field deviates granule is formed Three dimensional acoustic radiation masterpiece is 3 D captured field.For granule relative wavelength less when, acoustic radiation force is directly proportional to particle volume (for example, to radius cube be directly proportional).Acoustic radiation force is directly proportional to frequency harmony reduced factor.Acoustic radiation force is same and acoustic energy (such as sound pressure amplitude square) is proportional.For harmonic excitation, the sine space change of power drives granule to reach in standing wave Settling position.When the acoustic radiation force putting on granule is better than the collective effect of fluid drag power and buoyancy/gravity, in sound standing wave Field IT granule.Which results in the example being captured to concentrate, assemble and/or coalesce, then pass through Gravity Separation, will continue Ground drops out from multidimensional sound standing wave.Big side force makes the quick cluster of granule.Therefore, by enhanced Gravity Separation, a kind of The relatively large solid of material can divide from the relatively small granule of different materials, identical material and/or substrate fluid Separate out.
In this respect, reduced factor is particle and the compressibility of fluid itself and the difference of density.These characteristics are particles Feature with fluid itself.Compared with being suspended at medium therein with cell, the species of most cells show higher density and Lower compressibility, thus the sound reduced factor between cell and medium have on the occasion of.As a result, axial acoustic radiation force (ARF) drive the cell with positive reduced factor to go to pressure nodal plane, and drive cell with negative reduced factor or its His granule goes to pressure antinode plane.The radial direction of acoustic radiation force or cross component capture cell.The radial direction of ARF or cross component are big Collective effect in fluid drag power and gravity.Radial direction or cross component driving cell/granule are gone to them and can be collected as more The plane of big group, then will from fluid Gravity Separation.
When cell is assembled at the node of standing wave, equally occur that the physics of cell culture medium cleanses (scrubbing), This phenomenon is occurred by more captured cell contacts with having been held in standing wave inner cell.This phenomenon is substantially by cell Separate from cell culture medium.(expressed) biomolecule of expression is retained in nutrition liquor stream (i.e. cell culture medium).
For three-dimensional sound field, Gor ' kov formula can be used for calculating the acoustic radiation force F being applied to any sound fieldac.Basic Acoustic radiation force is defined as the function of field potential U,
Wherein field potential U is defined as
And f1And f2For one pole and dipole distribution, it is defined as
Wherein p is acoustic pressure, and u is fluid particle speed, and Λ is cell density ρpWith fluid density ρfRatio, σ is in cell Velocity of sound cpWith velocity of sound c in fluidfRatio, VoIt is the volume of cell, and<>Represent the time average within period of wave.Gor’ Kov formula is applied to the granule less than wavelength.For bigger particle size, Ilinskii provides for any particle size Calculate the equation of 3D acoustic radiation force.See Ilinskii, acoustic radiation force (the Acoustic Radiation on sphere in tissue Force on a Sphere in Tissue), Acoustical Society of America's magazine, 132,3,1954 (2012) (The Journal of The Acoustical Society of America, 132,3,1954 (2012)), this part is herein incorporated by reference this Literary composition.
In multimodal method (multimode fashion), the disturbance of piezoquartz in ultrasonic transducer allows to produce Multidimensional sound standing wave.Piezoquartz can be designed specifically under the frequency setting, and deform, this allow that many in multimodal method The generation of dimension sound standing wave.Multidimensional sound standing wave can be produced by the different mode of piezoquartz, and for example 3x3 pattern can produce multidimensional sound Standing wave.Again may be by allowing piezoquartz to vibrate through many different model shapes, produce most multidimensional sound standing waves. Therefore, crystal can encourage multiple patterns, such as 0x0 pattern (i.e. piston vibration pattern) to 1x1,2x2,1x3,3x1,3x3 with And the pattern of other higher order, then it is circulated back to the low mode (lower modes) (not necessarily pressing direct order) of crystal.Brilliant This conversion between modes of body or shake allow in setting time, and connection single-piston waveform is in interior multiple multidimensional The generation of waveform.
In present disclosure, single ultrasonic transducer includes the rectangular array of piezoelectric element, this array can operate to so that Some parts in array and the other parts out-phase in array.This equally can in fluid stream separation material.
One concrete application of sound swimming equipment is in the process of bioreactor material.In batch feeding bioreactor In (fed batch bioreactor) it is important that at the end of the production cycle expression material (expressed from liquor stream Materials all cells and cell debriss are filtered in).Expression material is made up of biomolecule, such as recombiant protein or Dan Ke Grand antibody, and it is intended to the desired product retaining.The use swum by sound, has effectively separated cell and cell debriss, And make the loss expressing material very low.This is that existing filtration treatment (depth-type filtration, tangential flow filtration, centrifugation) is changed Enter, existing filtration treatment shows limited efficiency when cell density is higher, thus, express the loss of material in filter bed itself May be up to by the 5% of the produced material of bioreactor.Including Chinese hamster ovary (CHO), NS0 hybridoma, young storehouse Ren Mus (BHK) cell and human body cell are in interior mammaliancellculture using it has proved that being to produce/expression (expressing) the very effective method of current recombiant protein needed for pharmacy and monoclonal antibody.Mammalian cell and The filtration that mammalian cell fragment is swum by sound, contributes to greatly improving the yield of fed-batch bioreactor.By many The use of dimension sound standing wave, sound swimming process equally can be attached thereto in the upstream of standard filtration process or downstream, such as with utilization Diatomaceous depth-type filtration, tangential flow filtration (TFF) or other physical filtering processes are connected.
Another type of bioreactor, irrigates reactor, employs the target protein from Chinese hamster ovary celI or monoclonal antibody Continuous expression.This makes the floor space in the faster production cycle less.Swum using sound in production/marking protein To keep Chinese hamster ovary celI to be very effective in fluid stream, and it is the production of closed loop manner.It has also allowed for protein With the largest production efficiency of monoclonal antibody, this is because there is no the material unaccounted-for (MUF) in filter bed.
In fed-batch biological reactor process, sound swimsuit is put and is captured cell and cell using single or multiple standing waves Fragment.There is cell and the mobile node to standing wave of cell debriss (with respect to antinode) of positive reduced factor.With cell with carefully Born of the same parents' fragment is assembled at the node of standing wave, equally occurs that the physics of cell culture medium cleanses (scrubbing), this phenomenon is passed through More captured cell contacts with having been held in standing wave inner cell occur.When the cell aggregation in multidimensional sound standing wave arrives When sound wave no longer can maintain the degree of cell aggregation block, the captured cell of gathering and cell debriss drop out stream due to gravity Body stream, and can separately receive.This is the time-continuing process of Gravity Separation.
Combined advanced many physical models and multiple dimensioned computer model and altofrequency, high power and high efficiency , ultrasonic drivers with embedded Control, to realize the new design of the acoustic resonator being driven by piezoelectric transducer array, produce Give birth to ability considerably beyond the sound swimming segregation apparatuss of current level.
It is desirable that such transducer produces three-dimensional standing wave in a fluid, this three-dimensional standing wave is with axial force to suspension Granule/second fluid applies side force, the particle capture ability of system so that increase sound is swum.The normally result announced in document is old Little two orders of magnitude of amplitude of the Amplitude Ration axial force of side force are stated.In contrast, technology disclosed herein provides Side force and axial force be equal magnitude.
System is driven by control signal and amplifier (not shown).System shows by computer monitor and control.Sometimes, Due to acoustic streaming (acoustic streaming) it may be necessary to modulate frequency and the voltage amplitude of standing wave.This can pass through amplitude Modulation and frequency modulation(PFM) complete.The dutycycle (duty cycle) that standing wave is propagated can be used for realizing the specific knot of material capture Really.In other words, acoustic beam can be opened and closed to realize expected result with different frequency.
The side force of the total acoustic radiation force (ARF) being generated by the ultrasonic transducer of present disclosure is reaching 2cm/s for overcoming High Linear speed and this speed on when fluid drag power be necessary and sufficiently.For example, by present disclosure device Linear speed for the separation of cell/granule, and can be up to 2cm/sec, for oils and fatss/water with minimum 4cm/min Separation phase.Flow velocity can be with minimum 25mL/min it is possible to up to 40mL/min to 1000mL/min, or even more high. For batch bioreactors, it is accurate for fed-batch bioreactor and perfusion bioreactor.
Show in Figure 1A for go oil removing or other be lighter than water material embodiment diagram.Applied by transducer 10 Driving frequency generally in from hundreds of KHz to tens of megahertz range.Form one between transducer 10 and reflector 11 Individual or multiple standing waves.At pressure antinode 14, in standing wave capture microdroplet 12, microdroplet 12 at pressure antinode 14 agglomeration, gathering, Caking or coalescence, and, in the case of buoyant material, float up to surface, and via the outflow above flow path Thing outlet 16 discharge.Purified water is discharged at outlet 18.Sound swimming isolation technics can complete multicomponent with the obvious cost reducing Grain separates, without dirty.
Show in Figure 1B for remove pollutant or other overweight water material embodiment diagram.By transducer 10 Apply the driving frequency generally in from hundreds of KHz to tens of megahertz range.At pressure node 15, catch in standing wave Obtain the pollutant flowing in water 13, these pollutant agglomeration, gathering, caking or coalescence at pressure node 15, and, heavier In the case of material, sink down into bottom collector, and via effluent outlet 17 discharge below flow path.Purify Water is discharged at outlet 18.
Usually, transducer is arranged as covering the whole cross section of flow path.In specific embodiment, Figure 1A or figure The sound swimming system of 1B has the square sectional of 6.375 inches of 6.375 inches of x, and it can be up to 5 gallons per minute in flow velocity (GPM) run, or in the case of linear speed up to 12.5mm/sec.Transducer 10 is PZT-8 (lead zirconate titanate) transducer, There is the square sectional of 1 inch of 1 inch of x and the resonant frequency of nominal 2MHz or 3MHz.Each transducer consumes the work(of about 60W Rate, to catch drop under the flow velocity as 5GPM for the flow velocity.This is converted to 0.500kW hr/m3Energy expenditure.This demonstrate this The at a fairly low energy consumption of technology.It is desirable that each transducer is powered and is controlled by its respective amplifier.One of present embodiment Application is by micron order size oil droplet agglomeration, assembles, lumps or be coalesced as significantly larger oil droplet, and changes particle size Distribution.
Fig. 2 is the sectional view of conventional ultrasonic transducer.This transducer has a wearing plate 50 in bottom, epoxy resin layer 52, Ceramic crystal 54 (being for example made up of PZT), epoxy resin layer 56 and backing layer 58.Respectively there is an electrode on ceramic crystal two sides： Anelectrode 61 and negative electrode 63.Backing layer 58 is attached to crystal 54 by epoxy resin layer 56.Whole assembly is contained in housing 60, Housing 60 can be made up of such as aluminum.Electric commutator 62 provide wire connection, with through housing and be attached to crystal 54 Lead (not shown) connects.Generally, backing layer is designed as increasing damping, and is formed in wider frequency range and has uniform displacement Wide-band transducer, and, be designed to certain vibration natural mode suppress excitation.Wearing plate is commonly designed as impedance conversion Device, preferably to mate the characteristic impedance of the medium that transducer is radiated.
Fig. 3 A is the sectional view of the ultrasonic transducer 81 of present disclosure, and ultrasonic transducer 81 can be used in sound swimming separator. Transducer 81 be shaped as disk or plate, and there is aluminum enclosure 82.Piezoquartz is crumby perovskite ceramics crystal, often Individual crystal include little, usually the quadrivalent metallic ion of titanium or zirconium in the lattice of big bivalent metal ion, divalent metal Ion is usually lead or barium, and O2-Ion.For example, PZT (lead zirconate titanate) crystal 86 limits the bottom of transducer, and exposes Outside in housing.Crystal is subject to supporting of small layer 98 in its periphery, and small layer 98 can be silicones or other classes As material, between crystal and housing.In other words, there is no wearing layer.
Via screw thread, the aluminum top board 82a of housing is attached to the body 82b of housing by screw 88.Top board include for The adapter 84 that transducer is powered.The top surface of PZT crystal 86 is connected to anelectrode 90 and negative electrode 92, and positive and negative electrode passes through insulation Material 94 is separately.Electrode can be made up of arbitrary conductive material, for example silver or nickel.By the electrode on crystal to PZT crystal 86 offer electrical power.Notice that crystal 86 does not have backing layer as shown in Figure 2 or epoxy resin layer.In other words, in transducer In, there is air gap 87 (this means, this air gap is entirely sky) between aluminum top board 82a and crystal 86.In some embodiments, permissible Minimal backing 58 and/or wearing plate 50 are set, as shown in Figure 3 B.
Transducer designs can affect the performance of system.Typical transducer is layer structure, with being bound to backing layer and resistance to The ceramic crystal of nog plate.Because loading on transducer by the high mechanical impedance that fluid presents, the traditional design with regard to wearing plate is accurate Then, for example the half-wavelength thickness for standing wave application or the quarter-wave thickness for radiation application, and manufacturer Method is possible and improper.By comparison, in a kind of embodiment of present disclosure, transducer there is no wearing plate or backing it is allowed to Crystal vibrates by having one of pattern of high Q factor in its natural mode.Ceramic crystal/the disc of vibration is directly exposed to flow through The fluid of flow chamber.
Removing backing (for example, making crystal air-backed) also allows ceramic crystal with less damping with higher order vibration mode Vibration (for example, higher order modal displacement).In the transducer with tape backing crystal, crystal with displacement vibration evenly, As piston.Removing backing be allow for crystal and vibrated with uneven displacement model.The mode of crystal gets over high-order, and crystal has more Many nodal lines.Although captured line need not correspond with the dependency of node, and, crystal is driven not necessarily with higher frequency Produce more captured line, but, the higher order modal displacement of crystal produces more captured line.See below with regard to Fig. 8 to figure The discussion of 9D.
In some embodiments, crystal can have bottom line affects the back of the body of crystal Q factor (for example, less than 5%) Lining.Backing can be made up of the material of abundant (substantially) entrant sound, such as cork wood, foam or cork, and it allows crystal With higher order modal vibration, and maintain high Q factor, still provide some mechanical support for crystal simultaneously.Backing layer can be solid , or, can be to there is the grid in the hole through this layer so that grid follows the vibration being in specific higher order vibration mode The node of crystal, provides while support it is allowed to the remainder free vibration of crystal at node position.Grid work piece or saturating The purpose of sound material is to provide to support, and does not reduce the Q factor of crystal, or the excitation of without prejudice to modality-specific.
Crystal is placed as and fluid directly contact, by avoiding damping and the energy absorption of epoxy resin layer and wearing plate Effect, equally can obtain high Q factor.Other embodiments are likely to be of wearing plate or wearing face to prevent containing lead PZT contact substrate fluid.For example in the biologic applications such as separating blood, this is probably desirable.Such application can With the wearing layer using such as chromium, electrolytic nickel or electroless.Equally can be using chemical vapor deposition to apply a strata (p- Asia dimethylbenzene) (poly (p-xylxyene)) (such as Parylene) or other polymer.Organic and bio-compatible applies Layer such as silicones or polyurethane also are used as wearing face.Equally can also be wear-resisting using vitreous carbon (glassy carbon) Layer.Vitreous carbon, also referred to as vitreous carbon, are a kind of ungraphitised carbons, and the performance of the performance of glass and pottery and graphite is tied by it Close.Most important performance is high temperature resistant, hardness high (7 Mohs), density is low, resistance is low, resistance is low and thermal resistance is low.Glass Glass carbon also has the resistance extremely strong to chemical erosion and the impermeability to gas and liquid.
In present disclosure, the form of piezoquartz used in each ultrasonic transducer is adjusted to the segmentation battle array of piezoelectric element The form of row.This array is used for forming the single or multiple multidimensional sound standing waves that can be used for sound swimming.
Fig. 4 is shown in entirety, the unipolar piezoquartz 200 of monolithic used in ultrasonic transducer.Piezoquartz There is substantially square shape, the length 203 having and wide by 205, long and width essentially identical (being for example about 1 inch).Brilliant Body 200 has inner surface 202, and crystal also has outer surface 204 in the reverse side of crystal, and this outer surface 204 is commonly exposed to flow The flowing that body is put by sound swimsuit.The area of outer surface and inner surface is relatively large, and crystal is relatively thin (for example brilliant for 2MHz Body, about 0.040 inch).
Fig. 5 shows the piezoquartz 200 ' of present disclosure.The inner surface 202 of piezoquartz 200 ' is cut into multiple The piezoelectric-array 206 of (i.e. at least two) piezoelectric element 208.However, array remains a monocrystal.Piezoelectric element 208 leads to Cross one or more raceway grooves or the otch in inner surface 202 210 is separated from each other.The width of raceway groove (i.e., between the piezoelectric elements) Degree can be about 0.0001 inch to about 0.02 inch of magnitude.The depth of raceway groove can be about 0.001 inch to about 0.02 English Very little.In certain embodiments, Embedding Material 212 (i.e. epoxy resin, silicon can be inserted in raceway groove 210 between the piezoelectric elements Glue (Sil-Gel) and similar material).Embedding Material 212 is non-conductive, as the insulator between adj acent piezoelectric element 208, Also there is the function that detached piezoelectric element 208 keeps together.Here, array 206 include 16 piezoelectric elements 208 (though So any amount of piezoelectric element is all possible), these piezoelectric elements 208 are arranged as rectangle 4x4 configuration (rectangle when square Subset).Each piezoelectric element 208 has and each roughly the same size.Whole array 200 ' has and the list shown in Fig. 4 Crystal identical length 203 and wide by 205.
Fig. 6 shows transducer 200 " another embodiment.Transducer 200 " is basic with the transducer 200 ' of Fig. 5 Similar, simply array 206 is formed with the configuration of 5x5 by 25 piezoelectric elements 208.Equally, whole array 200 " have with Monocrystal identical length 203 shown in Fig. 4 and wide by 205.
Each piezoelectric element in the piezoelectric-array of present disclosure can have independent point and connect (i.e. electrode), such that it is able to The frequency of each piezoelectric element independently controlled and power.These elements can share public ground electrode.Such configuration Not only allow for the formation of multidimensional sound standing wave, also allowed for improved sound standing wave and controlled.
Cut so that the surface of piezoquartz is divided into detached element by crossing a surface, piezoelectric-array can To be formed by overall piezoquartz.The cutting on surface can be by using saw, slotting cutter or other instruments, to remove the material on surface Expect and retain the discrete element of piezoquartz between the raceway groove/groove being consequently formed.
As explained above, composite will can be formed in the raceway groove/groove between Embedding Material embedded components.Example As for example, Embedding Material can be polymer, such as epoxy resin.In specific embodiment, each piezoelectric element 208 it Between have separate physical isolation.This structure can obtain by the following method：Insert Embedding Material in raceway groove 210, Then carry out cutting, sand milling and ground external surface 204, down to raceway groove.As a result, piezoelectric element passes through Embedding Material phase each other Connect, and each element is all the independent sector of array.In other words, by Embedding Material, each piezoelectric element and piezoelectricity about Element physical separation.Figure 21 is the sectional view comparing both embodiments.On top, show the crystal shown in Fig. 5.Including On surface 202, crystal is cut to four detached piezoelectric elements 208, but four piezoelectric elements share same outer surface 204.In bottom, four piezoelectric elements 208 pass through the mutual physical isolation of Embedding Material 212.Do not have common between four elements Surface.
In the present system, system is run under certain voltage, and such voltage makes granule be caught in ultrasonic standing wave Obtain, that is, be maintained at resting position.Granule is collected wherein along the captured line having limited, according to half-wavelength separately.In each node In face, granule is trapped at the minimum point of acoustic radiation potential energy.The axial component of acoustic radiation force drives and carries positive reduced factor Granule reach pressure nodal plane, and the granule carrying negative reduced factor is then driven to and reaches the pressure wave outside of belly.Acoustic radiation force Radial direction or cross component are the power capturing granule.In the system using typical transducer, the radial direction of acoustic radiation force or lateral point Measure several orders of magnitude generally little than the axial component of acoustic radiation force.However, the cross force in the separator of present disclosure can compare Substantially, it is in equal magnitude with axial force component, and enough to overcome linear velocity to be up to the drag of fluid during 1cm/s.As As discussed above, as the piston with uniform displacement, the vibration mode of effective exercise is contrary with crystal, by with higher Order mode state drives transducer, can increase cross force.Acoustic pressure is directly proportional to the driving voltage of transducer.Electrical power is flat with voltage Side is directly proportional.
In running, the piezoelectric-array of present disclosure can be driven so that the mutual homophase of piezoelectric element.In other words, respectively Piezoelectric element produces has same frequency and the multidimensional sound standing wave of no time shift.In other embodiments, piezoelectric element can phase Mutually out-phase, that is, they have different frequency or time shift, or there are different phase angles.Following article continuing on, More in specific implementation, the element arrangement in array is the group of out-phase or set, phase contrast be 90 ° of multiple (i.e. 90 ° and/or 180 °).
In certain embodiments, the pulse voltage signal of transducer is driven can to have sine wave, square wave, sawtooth waveforms or three The waveform of angle ripple, and there is 500 kilo hertzs to 10 megahertzs of frequency.Pulse voltage signal can with pulse width modulation (PWM, Pulsewidth modulation) drive, pulse width modulation can produce the waveform of any desired.Pulse voltage signal can also have amplitude modulation or Frequency modulation starts/stopping ability, to eliminate acoustic streaming.
Fig. 7 is log-log image (y-axis and x-axis are logarithmic axis), shows acoustic radiation force, fluid drag power and granule The yardstick of radius buoyancy.Calculating completes for SAE-30 oil droplet typical used in experiment.Buoyancy is and particle volume Related power, so for the particle size of micron dimension, buoyancy can be ignored, but is as particle size growth, for number The particle size of hundred micron dimensions, buoyancy becomes more obvious.Fluid drag power and fluid velocity linearly, so for The granule of micron dimension size, fluid drag power would generally exceed buoyancy, but the larger particles for hundreds of micron dimension sizes, Fluid drag power can be ignored.The yardstick (scaling) of acoustic radiation force is different.When the particle size becomes smaller, Gor ' kov formula is accurate True, sound force trapping is proportional to particle volume.Finally, when particle size growth, acoustic radiation force is no longer with particle volume half Cube growth in footpath, and will rapidly disappear in specific critical particle size.Continuation for particle size increases, radiant force Amplitude increases again, but its opposite in phase (not shown in the picture).This pattern repeats, in order to increase particle size.
Initially, when dispersion (suspension) mainly flows through system with the little particle of micron-scale, in order to stay Granule is captured, acoustic radiation force needs balanced fluid drag and the collective effect of buoyancy in ripple.In the figure 7, this situation occurs When particle size is about 3.5 microns, it is labeled as Rc1.Then image points out that all bigger granules also can be captured.Therefore, when When little particle is trapped in standing wave, there occurs agglomeration, gathering, caking or the coalescence of granule, cause holding of granule effective dimensions Continuous growth.When particle size growth, acoustic radiation force reflects at granule, thus bulky grain can lead to the minimizing of acoustic radiation force. Particle size continues to increase, and until buoyancy starts to play a leading role, this o'clock is by the second critical particle size Rc2Point out, critical at this During particle size, granule floats or sinks to depending on their relative densities with regard to substrate fluid.When granule floats or sinks, They no longer reflect acoustic radiation force, thus acoustic radiation force increases once again.And not all granule all can drop out, these remainder particulate Size also will continue to increase.This phenomenon explains oversize R in the figure 7c2The rapid decrease of acoustic radiation force and rising afterwards.Cause This, Fig. 7 explains how persistently to capture little particle in standing wave, and how little particle gathers into bulky grain or clump, Ran Houyou Continue to drop out from multidimensional sound standing wave in Gravity Separation.
The size of transducer, shape and thickness determine the displacement of transducer under the excitation of different frequency, and this displacement is again Have impact on separating of oil efficiency.Generally, transducer runs under the frequency near thickness resonance frequency (half-wavelength).Transducer position The gradient moved typically results in oil and is trapped in multiple positions.The displacement of high order mode produces all directions in sound field and carries ladder more by force The three-dimensional sound standing wave of degree, thus creating acoustic radiation force strong on an equal basis in all directions, which results in many captured line, captured line Quantity is related to the concrete mode of transducer.
Fig. 8 shows the resistance of 1 square inch of PZT-8 2-MHz of measurement in 2.2MHz transducer near resonance frequency Anti- amplitude is with regard to the function of frequency.The acoustic resonance of the corresponding water column of the minimum point of transducer electrical impedance, and represent potential fortune Line frequency.Numerical model is pointed out, under these resonant frequencies, the distribution of transducer displacement occurs significantly to change, thus directly Have impact on sound standing wave and the force trapping producing.Because transducer operates in the vicinity of its thickness resonance frequency, the position of electrode surface Moving is substantially out-phase.Generally, the displacement of transducer electrode is uneven, and is changed according to driving frequency.For example, one Under the individual driving frequency carrying a capture oil droplet line, displacement has the single maximum of points entreated in the electrodes, and has and changing The minimum point of energy device adjacent edges.Under other driving frequencies, transducer section has multiple maximum of points, which results in many Individual oil droplet captured line.High-order transducer displacement pattern causes higher force trapping and multiple stable capture for capturing oil droplet Line.
In order to study the distribution (profile) of the transducer displacement effect to sound force trapping and oil droplet separation efficiency, will be real Test and be repeated ten times, in addition to driving frequency, all conditions of experiment are all identical every time.In fig. 8, ten adjacent resonance Frequency is indicated with encircled numbers 1 to 9 and alphabetical A, and this ten resonant frequencies are used as driving frequency.These vibrations of impedance are right The resonance of Ying Yusheng swimming system.When the length of sound swimming system is 2 inches, vibration is divided out with being spaced about 15kHz.Experiment condition is The experiment duration of 30 minutes, the oil concentration of 1000ppm of about 5 microns of SAE-30 oil droplets, the flow velocity of 500 ml/min, Yi Ji The applying power of 20W at 2 inches of long sections of 1 inch wide x.
Pass through transducer with emulsion it was observed that the captured line of oil droplet make its characterization.With regard to identified in Fig. 8 In ten resonant frequencies seven, characterization is related to cross the observation of captured line quantity of runner and the feature of its pattern, such as Shown in Fig. 9 A.
Fig. 9 B illustrates the isometric side view of the system, wherein determines capture line position.Fig. 9 C is the system along arrow 114 The figure that when overlooking entrance, the system is presented.Fig. 9 D be along arrow 116 directly observe energy converter planar when the figure that presented of the system. Captured line shown in Fig. 9 B to 9D is that the frequency 4 times in Fig. 8 and Fig. 9 A is produced.
The impact of driving frequency has been determined clearly the quantity of captured line, and the quantity of captured line is from acoustic resonance driving frequency Wall scroll captured line under 5 and 9 is changed to 9 captured line under acoustic resonance frequency 4.It was observed that 4 under other driving frequencies Or 5 captured line.The different Displacements Distribution of transducer can produce the captured line of different (more) in standing wave, and in Displacements Distribution Bigger gradient typically set up higher force trapping and more captured line.
Table 1 is summarized and derives from the discovery being obtained experiment using the oil trap of the system similar to Figure 10 A.One important conclusion is, The separating of oil efficiency of sound separator is directly related with the mode of transducer.The Displacements Distribution of more high-order produces bigger sound force trapping With more captured line, lead to higher efficiency.Useful second is studied to yardstick (scaling) it was concluded that test shows, Capture 5 microns of oil droplets with 500 ml/min, every 1 inch of acoustic beam span, per square inch transducer area need 10 watts of power. Main consume is the consume that the thermal viscosity in the cumulative volume of sound standing wave absorbs.Energy cost under this flow velocity is every cubic metre 0.500 kilowatt hour.
Table 1：Acquisition mode capture efficiency research
Show the medium-scale device 124 of a kind of 4 inches × 2.5 inches of flow cross section area in Figure 10 A, be used for Separate substrate fluid and floating fluid or granule.Sound passage length is 4 inches.Here, this device is illustrated at flow direction Downward orientation, this is used for separating low-density particles from substrate fluid.However, substantially, this device can turn upside down, with Allow to separate the granule overweighting substrate fluid.Different from direction buoyancy upwards, due to gravity, the weight of agglomerated particle pulls it Downwards.It should be noted that present embodiment is depicted as thering is the orientation that fluid is flowed in vertical mode.However, it is also possible to Consider, fluid flows with horizontal direction or at a certain angle.
Fluid containing granule enters this device by entrance 126, enters into annular pressure chamber (annular plenum) In 131.Annular pressure chamber has circular inside diameters and annular external diameter.Note, here, between " annular " two shapes for finger of term Region, pressure chamber is not necessarily circle.Two entrances can be seen but it is also possible to be arranged as required to Arbitrary Digit in here diagram The entrance of amount.In a particular embodiment, four entrances are employed.These entrances are radial opposed and are orientated.
Special-shaped ozzle wall 129 reduces the external diameter of stream by this way, is producing higher speed near the region of wall And reduce turbulent flow, it is distributed development with fluid velocity and produces adjacent piston stream, it is, making fluid add downwards along center line direction Speed, only carries seldom even without circumferential movement component and relatively low flow turbulence.This generates a kind of for sound separate with And the room flow distribution that powder collection is optimum.Fluid passes through connecting tube 127, and enters flowing/separation chamber 128.In Figure 10 B shape tube Can see in the enlarged drawing of mouth 129, ozzle wall also adds radial motion component to particle, make granule mobile and closer to In the center line of this device, and produce more collisions with the agglomerated particle rising, float.Before reaching separation chamber, connecting In pipe 127, this radial motion permission granule most preferably cleanses (scrubbing) with fluid.Special-shaped ozzle wall 129 is with such as lower section Formula guides fluid, produces extensive vortex in the porch of collecting pipe 133, thus also improving the collection of granule.Generally, device 124 flow region is designed to persistently reduce from annular pressure chamber 131 to separation chamber 128, to ensure turbulent flow with the formation being vortexed relatively Few, in order to the separation of more preferable granule, agglomeration and collection.Ozzle wall has wide end and narrow end.Term is cleansed for description The agglomeration of grain/drop, the process of gathering, caking or coalescence, this process is in larger particles/drop along the direction contrary with flow of fluid Upper occur when moving and colliding with smaller particle, its effect is to cleanse suspension by smaller particle.
Return to Figure 10 A, flowing/separation chamber 128 includes transducer array 130 and the reflector of the opposite sides positioned at this room 132.In use, multi-dimensional standing-wave 134 produces between transducer array 130 and reflector 132.These standing waves can be used to agglomeration Granule, and this granule (for example, oil) being orientated for agglomeration floating.Then, the fluid containing residual particles is gone out by fluid Mouth 135 outflow.
With floating particles agglomeration, they finally overcome flow of fluid drag and the collective effect of acoustic radiation force, and Their buoyancy be enough to promote floating particles to rise.At this on the one hand, collecting pipe 133 is surrounded by annular pressure chamber 131.Larger Granule will be managed by this and be entered collecting chamber 140.This collecting chamber can also be a part for outlet.Collecting pipe and fluid issuing Opposite end positioned at device.
It should be noted that the floating particles formed in separation chamber 128 subsequently pass through connecting tube 127 and ozzle wall 129.By Applied radially to move in ozzle wall, this leads to flow through the agglomerated particle of rising from becoming a mandarin of annular pressure chamber.
The transducer configuration of present disclosure creates three-dimensional pressure field, and this three-dimensional pressure field includes staying perpendicular to flow of fluid Ripple.Barometric gradient is sufficiently large it is sufficient to generation is orthogonal to the sound swimming power (i.e. sound swimming power is parallel to fluid flow direction) in standing wave direction, Its amplitude is equal magnitude with the amplitude of the sound swimming power along wave direction.This allows the enhanced capture in flow chamber with along good restriction The particle capture of line and collection, contrary with only capturing granule in conventional equipment like that in collection surface.When granule has enough Between shift to node or the antinode of standing wave, create granule can concentrate, agglomeration and/or coalescence, the then area of buoyancy/Gravity Separation Domain.
In some embodiments, flow of fluid has up to 1500 Reynolds number (Reynolds number), it is, laminar flow Occur.For industrial practical application, for the flowing flowing through the system, Reynolds number often from 10 to 1500.Granule creates the Reynolds number far below 1.0 with respect to the movement of fluid motion.Reynolds number is represented to constant current The ratio of inertia flowing effect and viscous effect in.For the Reynolds number less than 1.0, viscous force in flow field predominantly Position.This leads to significantly damp, and in whole flowing, shearing force is preponderated.The dominant this flowing of viscous force is referred to as Stokes Stream.The flowing of molasses is a kind of example.Under these conditions, wall profile controls and streamlining only has slight influence.This with Flowing in the very viscous flowing of fluid or very minim channel such as MEMS device is associated.The control tool of inlet profiles There is slight influence.In sound swimming particle separator, granule will be Stokes stream with respect to the flowing of fluid, this is because granule is straight Relative velocity between footpath and granule and fluid all very littles.On the other hand, with regard to flowing through the Reynolds of the flowing of the system Number will be much larger than 1.0, this is because fluid velocity is all relative with inlet diameter much larger.
For the Reynolds number much larger than 1.0, the local viscous force only being contacted with surface in stream is only predominantly Position.This sticky region near surface is referred to as boundary region, and first recognizes that (list of references by Ludwig Prandtl 2).In pipeline stream, for the stream of the formation completely in pipeline, if Reynolds number apparently higher than 1.0 and is less than 2300, then this stream will be laminar flow.Wall shearing stress at wall will diffuse into distance in becoming a mandarin.In the porch of pipeline, with equal Even flow velocity starts.Move down along pipeline with flowing, the effect of wall viscous force towards center line to internal diffusion, and will produce throwing Thing linear velocity is distributed.This parabolic distribution will have peak value, and this peak value is the twice of average speed.The formation of parabolic distribution Required length is the function of Reynolds number.(this Reynolds number is allusion quotation for CHO operation to Reynolds number for 20 Type), forming length is 1.2 times of pipe diameters.Therefore, the flowing of formation completely occurs very fast.This peak value at center It can be unfavorable that speed separates to sound granule.Equally, at laminar flow, Reynolds number turbulent flow is likely to occur, and, flow surface It is very important that profile controls in terms of controlling flowing.For these reasons, described separator is designed with annular to enter Mouth pressure chamber and collecting pipe.
It is connected to entry wall ozzle, fluid is accelerated and inwardly guides towards center line, as Figure 10 B institute by it after big annular pressure chamber Show.Wall profile has considerable influence to distribution.Region convergence increased the average speed of stream, but wall profile determines VELOCITY DISTRIBUTION. Ozzle wall profile will be fairshaped, and be designed with less radius of curvature in the separator.
Transducer is used for producing pressure field, and this pressure field all produces on standing wave direction with the direction being orthogonal to standing wave direction Order of magnitude identical power.When these power are substantially equal magnitude, a size of 0.1 micron to 300 microns of granule will more have Effect ground is towards agglomeration area (" captured line ") motion.In the force component because orthogonal sound is swum, the gradient of equal amplitude, has " focus " or granule Collecting region, its not rotine positioning on standing wave direction between transducer 130 and reflector 132.Focus is located at acoustic radiation potential energy Minimum point.This focus represents powder collection position.
A kind of application of this sound swimming separator is to isolate Biotherapeutics from the biological cell producing Biotherapeutics albumen Albumen.In this respect, existing separation method requires to filter or is centrifuged, and both can damage cell in both, discharges albumen Matter fragment and enzyme enter purification process, and increase the burden to purification system downstream part.It is desirable that can process having more The volume of high-cell density, because this allows collecting and higher cost benefit of more substantial therapeutic protein.
Figure 11 A and Figure 11 B is the exploded view illustrating sound swimming separator each several part.Figure 11 A only one of which separation chamber, and scheme 11B has Liang Ge separation chamber.
Reference picture 11A, fluid enters separator 190 by four port ingress 191.Here it is seen that annular pressure chamber.Setting Transition piece 192 is to set up the piston flow by separation chamber 193.This transition piece includes such as Figure 10 A and as described above, has curved The special-shaped ozzle wall of curved shape.Transducer 40 and reflector 194 are located in the opposite wall of separation chamber.Then, fluid passes through outlet 195 discharge from separation chamber 193 and separator.Separation chamber has the stream geometric construction of rectangular shape.
Figure 11 B has Liang Ge separation chamber 193.System connection device 196 is located between two rooms 193, and two rooms 193 are tied Altogether.
The sound detached test of swimming has been carried out for different Chinese hamster ovaries (CHO) cell line.In an experiment, use As the system described in Figure 11 A, to having 8.09 × 106The initial cell density of cells/ml, 1,232NTU turbidity, And the solution of cell viability about 75% is separated.Transducer is 2MHz crystal, runs on about 2.23MHz, consume 24～ 28 watts.Employ the flow velocity of 25 ml/min.The result of this experiment is shown in Figure 12 A.
In another experiment, to having 8.09 × 106The initial cell density of cells/ml, 1,232NTU turbidity, with And the solution of cell viability about 75% is separated.This Chinese hamster ovary celI cording has bimodal particle size distribution (in 12 microns of size At 20 microns).Result is shown in Figure 12 B.
Figure 12 A and Figure 12 B is to be produced by Beckman Kurt (Beckman Coulter) cell viability analyser.Its It is tested and discloses：When separating cell from fluid, it is effective that the frequency of 1MHz and 3MHz is not so good as 2MHz.
In the other tests with 10 ls/h of flow velocitys, capture 99% cell, and confirm that cell viability is higher than 99%.With 50 ml/min (i.e.：3 ls/h) in other tests of flow velocity, obtain 3 × 106Cells/ml final Cell density, and there is the vigor close to 100%, and almost do not have temperature to rise.Other test in, 6 liters/little When flow velocity under, obtained 95% turbidity reduce.
It is used yeast as the analogies of CHO, biologic applications have been carried out single with regard to demarcating shown in Figure 10 A to 10B The test of unit.For these tests, under 15 ls/h of flow velocitys, test different frequency and different capacity level.Table 2 shows Go out the result of test.
Table 2：The result of the system of 4 inches of the lower 2.5 inches of x of 15 ls/h of flow velocitys
Frequency (megahertz) 30 watts 37 watts 45 watts
2.2211 93.9 81.4 84.0
2.2283 85.5 78.7 85.4
2.2356 89.1 85.8 81.0
2.243 86.7 - 79.6
In biologic applications, many parts, for example, lead to or from housing, entrance, discharge pressure room and enter pressure The connecting tube of room etc. can be disposable, and only transducer and reflector will be cleaned for reusing.Avoid Centrifuge and filter it is allowed to Chinese hamster ovary celI preferably separates, without reduce cell vigor.Sound swim separator shape because Son again smaller than filtration system form factor it is allowed to CHO detached miniaturization.Transducer can also be actuated to be formed quickly Pressure change, to avoid or to remove due to the obstruction of Chinese hamster ovary celI agglomeration.The frequency of transducer can also change, to obtain Best available property under given power.
Embodiment is provided below, so that device, part and the method for present disclosure to be described.These embodiments are only illustrative, The material, condition or the procedure parameter that cannot be used for limiting present disclosure are material disclosed below, condition or procedure parameter.
Embodiment
Using COMSOL simulation software, it is that sound swimsuit is put and established two-dimensional mathematical model.This model is as shown in figure 13.Device Rustless steel reflector 224 including aluminum wall 222 with positioned at offside wall.Piezoelectric transducer 230 is embedded in wall.As noted herein , the form of transducer is 4 element piezoelectric-arrays.Wall 222 and reflector 224 define flow chamber, and wherein arrow 225 designates stream The flow direction by flow chamber for the body.Piezoelectric transducer and fluid directly contact.Even if in simulations not using Embedding Material, equally showing Raceway groove/otch 210 and Embedding Material 212 are gone out.
Run simulation software, and output it with disclosed data (Barmatz, J.Acoust.Soc.Am.77,928, 1985) contrasted.Figure 14 A compares momentum U.Figure 14 B compares the x-component of acoustic radiation force (ARF).Figure 14 C compares ARF Y-component.Figure 14 D compares the absolute value of ARF.In these figures, top is public data, and bottom is the knot of numerical model Really.As illustrated, the result of numerical model is corresponding with public data, this demonstrates numerical model and the rear reforwarding thus carrying out Calculate.
Then run three different emulation, with set up using three kinds of different piezoelectric transducers by SAE 30 oil droplet from Detached model in water.Three kinds of piezoelectric transducers are respectively：1 element transducer (i.e. monocrystal), 4 element transducer and 5 elements Transducer.These transducers run on identical frequency, and, oil and water use following parameter：Oil particles radius (RP)= 10μm；Oil density (ρp)=865kg/m3；The velocity of sound (c in oilp)=1750m/sec；Particle speed (μf)=0.001kg/m sec；Water density (ρf)=1000kg/m3；And the velocity of sound (the c in waterf)=1500m/sec.
For 4 element transducer, each raceway groove has 0.0156 inch of width and 0.0100 inch of depth, and respectively Element has 0.2383 inch of width (overall width of transducer is an inch).For 5 element transducer, each raceway groove has The depth of 0.0156 inch of width and 0.0100 inch, and each element has 0.1875 inch of width.
Figure 15 shows the emulation using numerical density during 1 element transducer, is the two-dimensional representation of PZT crystal 200.Figure 16 Show the emulation using numerical density during 4 element transducer, be the two-dimensional representation of PZT crystal 200 '.Figure 17 shows and uses 5 The emulation of numerical density during element transducer, is PZT crystal 200 " two-dimensional representation.Each transducer has identical width, with The number of elements that it has is unrelated.It will be clear that amplitude (the light-colored area of the multidimensional sound standing wave producing from transducer The amplitude in domain is higher than saturate region).
Then run emulation on 4 element arrays, to compare the effect of phase place on ripple.Flow velocity is 500 ml/min, stream The Reynolds number of body is 220, and the input voltage of each element is direct current 2.5V, and the dc power of each element is 1 watt Special.In an emulation, in the relatively each leisure 0-180-0-180 phase place of four elements (i.e. out-phase).In another emulation, four Mutual homophase between element.Then emulation is compared with the actual experiment being carried out with the transducer mount with 4x4 piezoelectric-array, such as Shown in Figure 18.
When Figure 19 compares transducer mount in Figure 18 and uses out-phase array, the result (left) of out-phase emulation and illustrate reality The figure (right) of result.Result is closely similar.The higher position of amplitude in simulations, can see in the corresponding position of actual figure The granule of capture.
When Figure 20 compares ring energy device in Figure 18 and uses homophase array, the result (left) of homophase emulation and illustrate reality The figure (right) of result.Result is closely similar.
For 4 element transducer and 5 element transducer, for 20 microns of oil droplet of diameter, in 2.19MHz to 2.25MHz Frequency sweep under, run homophase under different arrangements for the other numerical model and out-phase emulation, described in table 3 in following article.Different The meaning of phase is with the adjacent element of different phase excitations.
Figure 22 shows two kinds of out-phase patterns for 4 element arrays emulation.Left figure illustrates 0-180-0-180 pattern, and Right figure illustrates 0-180-180-0 pattern.Figure 23 shows four kinds of out-phase patterns for 5 element arrays emulation.Upper left illustrates 0-180-0-180-0 pattern.Upper right illustrates 0-0-180-0-0 pattern.Lower-left illustrates 0-180-180-180-0 pattern.Right Under illustrate 0-90-180-90-0 pattern.
In this frequency range, determine the cross component (x-axis) of acoustic radiation force and the ratio of axial component (y-axis), this ratio The scope of value is listed in following table 3.
Table 3
Transducer Phase place Minimum ratio Maximum ratio
1 element (monocrystal) ～0.15 ～0.75
4 element arrays Homophase ～0.08 ～0.54
4 element arrays (0-180-0-180) ～0.39 ～0.94
4 element arrays (0-180-180-0) ～0.39 ～0.92
5 element arrays Homophase ～0.31 ～0.85
5 element arrays (0-180-0-180-0) ～0.41 ～0.87
5 element arrays (0-0-180-0-0) ～0.41 ～0.81
5 element arrays (0-180-180-180-0) ～0.40 ～0.85
5 element arrays (0-90-180-90-0) ～0.38 ～0.81
Figure 24 illustrates the normalized acoustic radiation force (ARF) from the emulation of single piezoquartz.By by measurement voltage and The real power that galvanometer calculates, by the value normalization of ARF.Figure 25 shows and imitates in test frequency scope for single piezoquartz Very, the ratio of ARF component (laterally and axially).Figure 26 illustrates the normalization acoustic radiation force from 5 element emulation.Figure 27 shows For the 5 element emulation in test frequency scope, the ratio of ARF component (laterally and axially).Relatively Figure 24 and Figure 26,1 element The ARF peak value of emulation is about 6e-11, and the ARF peak value of 5 element emulation is about 2e-9.Relatively Figure 25 and Figure 27, power in Figure 27 Ratio is also more stable (consistent), and Figure 25 has about 0.60 variation, and Figure 27 has about 0.40 variation.
Generally, 4 elements and 5 element arrays produce higher ratio, including the ratio more than 0.9.Also have in some emulation The acoustic radiation force amplitude (acoustic radiation force that 1 element produces is as baseline) of big almost two magnitudes producing than 1 element transducer.
Then 16 elements and the experimental array of 25 elements are tested.The solution flowing into is 3% tytosis cake yeast solution (packed cell mass yeast solution), with acting on the analogies of the Chinese hamster ovary celI of biologic applications.For out-phase Test, employs the checker board pattern of 0 ° and 180 ° phase angle.For 25 element arrays, the phase place of 12 elements is 180 °, 13 units The phase place of part is 0 °.Figure 28 shows these checker board pattern.The left side is 16 element arrays, and the right is 25 element arrays, different The different phase angle of shadow representation.
At 30 minutes of different frequency afterwards, the turbidity of measurement influent, concentrated solution and penetrating fluid.Concentrated solution is to flow out The part containing concentration yeast of device is together with some fluids.Penetrating fluid is the filtered part of bleeder, and it is most of For liquid, the yeast with very little concentration.Relatively low turbidity represents relatively low yeast concentration.According to (influent-penetrating fluid)/ Influent * 100% determines capture rate.The flow velocity of influent is 30 ml/min, and the flow velocity of concentrated solution is 5 ml/min. The power setting of transducer is 8W.
Table 4 lists the result of one-element transducers, and it is used for as baseline or control line.
Table 4
Frequency (megahertz) 2.225 2.244
Concentrated solution (NTU) 15,400 15,400
Penetrating fluid (NTU) 262 327
Influent (NTU) 4,550 5,080
Capture rate (%) 94.2 93.6
Table 5 lists the experimental result of 16 element transducer homophases.
Table 5
Frequency (megahertz) 2.22 2.225 2.23 2.242 2.243 2.244 2.255 2.26
Concentrated solution (NTU) 22,700 24,300 22,500 24,600 23,100 28,100 27,400 23,800
Penetrating fluid (NTU) 205 233 241 201 249 197 244 165
Influent (NTU) 5,080 4,850 5,100 4,830 4,810 5,080 4,940 4,830
Capture rate (%) 96.0 95.2 95.3 95.8 94.8 96.1 95.1 96.6
Table 6 lists the experimental result of 16 element transducer out-phase.
Table 6
Frequency (megahertz) 2.22 2.225 2.23 2.242 2.243 2.244 2.255 2.26
Concentrated solution (NTU) 40,900 21,400 26,000 49,300 19,100 55,800 22,100 35,000
Penetrating fluid (NTU) 351 369 382 1,690 829 761 397 581
Influent (NTU) 5,590 4,870 5,860 5,160 5,040 4,870 4,800 5,170
Capture rate (%) 93.7 92.4 93.5 67.2 83.6 84.4 91.7 88.8
The result of 16 element arrays is compared to each other, and compares with matched group, homophase array maintains in frequency range High capture rate, and the capture rate of out-phase array starts rapid decrease at about 2.24MHz.Most of homophases are surveyed Examination, the result of efficiency is much like with matched group.In each frequency, the efficiency of homophase is all than the efficiency high of out-phase.
Table 7 lists the experimental result of 25 element transducer homophases.
Table 7
Frequency (megahertz) 2.2190 2.2300 2.2355 2.2470 2.2475 2.2480 2.2485 2.2615
Concentrated solution (NTU) 13,300 19,800 20,900 21,400 13,700 17,300 19,000 19,500
Penetrating fluid (NTU) 950 669 283 1,044 1,094 1,164 688 797
Influent (NTU) 4,930 4,930 4,910 5,010 4,950 5,220 5,010 5,110
Capture rate (%) 80.7 86.4 94.2 79.2 77.9 77.7 86.3 84.4
Table 8 lists the experimental result of 25 element transducer out-phase.
Table 8
Frequency (megahertz) 2.2190 2.2300 2.2355 2.2470 2.2475 2.2480 2.2485 2.2615
Concentrated solution (NTU) 14,605 - 21,700 18,025 23,425 22,575 21,900 22,450
Penetrating fluid (NTU) 2,568 2,541 1,484 1,134 1,005 987 905 2,034
Influent (NTU) 5,610 6,020 5,200 6,010 5,880 5,840 5,860 5,880
Capture rate (%) 54.2 57.8 71.5 81.1 82.9 83.1 84.6 65.4
The result of 25 element arrays is compared to each other, and compares with matched group, both efficiency is all low than matched group.25 yuan Part homophase array peak value is about 95%, then all falls in both direction.Out-phase array peak value is about 85% efficiency, and drastically Decline.The result of efficiency is closely similar with matched group.It should be noted that not having for the peak value amplitude being found using numerical model Have and carry out experiment test.
With reference to illustrative embodiments, present disclosure is described.Obviously, reading and understanding aforementioned specific descriptions Afterwards, other people can make modifications and changes.It is intended to present disclosure is construed to including all such modifications and change, as long as this A little modifications and changes are within the scope of claims or its equivalent.

Claims (20)

1. a kind of device for separating second fluid or granule from substrate fluid, it includes：
Flow chamber, it has at least one entrance and at least one exports；
At least one ultrasonic transducer, it is located on the wall of described flow chamber, and described transducer includes piezoelectric-array, and it is by multiple pressures Electric device is formed, and described piezoelectric element can be driven by voltage signal, to produce multidimensional sound standing wave in described flow chamber；And
At least one reflector, its be located at described flow chamber in the wall of at least one ultrasonic transducer opposite side described on.
2. device according to claim 1, wherein said piezoelectric-array is present on monocrystal, by one or more ditch Described piezoelectric element is separated from each other by road.
3. device according to claim 2, the Embedding Material being wherein different from described piezoelectric is present in described one Or in a plurality of raceway groove.
4. device according to claim 3, wherein said Embedding Material is epoxy resin.
5. device according to claim 1, wherein each piezoelectric element is divided by Embedding Material physics with the piezoelectric element of surrounding From.
6. device according to claim 1, wherein said piezoelectric-array is rectangular array.
7. device according to claim 1, wherein each piezoelectric element is of the same size.
8. device according to claim 1, independently own with it electrode pair of wherein each piezoelectric element is connected.
9. device according to claim 1, wherein special-shaped ozzle wall is located at the upstream of at least one entrance of described flow chamber.
10. a kind of method separating second fluid or granule from substrate fluid, including：
Described substrate fluid and the mixture of described second fluid or granule is made to flow through device, described device includes：
Flow chamber, has at least one entrance and at least one exports；
At least one ultrasonic transducer, it is located on the wall of described flow chamber, and described ultrasonic transducer includes piezoelectric-array, and it is by many Individual piezoelectric element is formed, and described piezoelectric element can be driven by voltage signal, to form multi-dimensional standing-wave in described flow chamber；With And
At least one reflector, its be located at described flow chamber in the wall of at least one ultrasonic transducer opposite side described on；And
Send voltage signal to described piezoelectric-array, to form multidimensional sound standing wave, it is described that it resists the flowing capture of described fluid Second fluid or granule, it is allowed to assemble at pressure node, thus the size of described second fluid or granule increases, and pass through weight Power separates, and constantly drops out from described multidimensional sound standing wave.
11. methods according to claim 10, wherein said granule is Chinese hamster ovary (CHO) cell, NS0 hybridoma Cell, baby hamster kidney (BHK) cell or human body cell.
12. methods according to claim 10, the mutual out-phase of wherein said piezoelectric element is run.
13. methods according to claim 10, the mutual inphase operation of wherein said piezoelectric element.
14. methods according to claim 10, are wherein at least 25 by the flow velocity of the described substrate fluid of described flow chamber Ml/min.
15. methods according to claim 10, frequency fortune in the range of 100kHz to 20MHz for the wherein said piezoelectric element OK.
16. methods according to claim 10, wherein said multidimensional sound standing wave causes acoustic radiation force, described acoustic radiation force tool The amplitude of some axial components and cross component is in same magnitude.
17. method according to claim 10, wherein said piezoelectric-array is present on monocrystal, by one or more Described piezoelectric element is separated from each other by raceway groove.
18. methods according to claim 17, the Embedding Material being wherein different from described piezoelectric is present in described one In bar or a plurality of raceway groove.
The piezoelectric element of 19. methods according to claim 10, wherein each piezoelectric element and surrounding is by Embedding Material physics Separate.
20. methods according to claim 10, independently own with it electrode pair of wherein each piezoelectric element is connected.
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